This invention relates to immunoglobulin adsorbents and apparatus for adsorbing immunoglobulins using such adsorbents useful in the treatment of various diseases including autoimmune diseases such as myathenia gravis, articular rheumatism, lupus erythematosus, etc., immunity-related diseases such as glumerulonephritis, bronchial asthma, polyneuritis, etc., organ transplantation such as transplanted kidney rejection, AOB incompatible bone marrow transplantation, etc., tumor, hypertension, and hepatic insufficiency.
In recent years, plasma exchange therapeutics have been employed for the purpose of treating autoimmune diseases, immunity-related diseases, organ transplantation, tumor, hypertension, hepatic insufficiency and other diseases. In the plasma exchange therapeutics, however, all the plasma components are indiscriminately removed so that useful components in plasma are lost. Several problems are pointed out including shortness of useful components in plasma or plasma preparations used as a make-up and probable complication of serum hepatitis and allergy. It is thus believed desirable to depurate the patient's own plasma before it is transfused.
A variety of methods have been devised for removal of pathogenic substances, for example, cascade method using a membrane filter (see H. G. Sieberth, Plasma Exchange, p. 29, F. K. Schattauer Verlag, Stuttgart-New York, 1980), double filtration (see, Tetsuzo Agishi et al., Kidney and Dialysis, 10(3), 475, 1981), freeze filtration (A. L'Abbate et al., Proc. Eur. Dial. Transplant. Assoc., 14, 486, 1977), and plasma salting-out treatment (see, Oe Hiroaki et al., Artificial Organs, 14(1), 472, 1985). These methods are on the way of clinical trial.
However, removal of unnecessary pathogenic substances is insufficient under the current circumstances. Clinical application will invite hypoproteinemia unless plasma make-up is used.
Other therapeutics are by the use of various medicines. Because of probable side-effects, a careful attention must be paid to their use. For example, their dose and administration period should be limited as low as possible.
There is the need for a depurant and depuration apparatus capable of selectively adsorbing and removing particular pathogenic substances in plasma without inducing a side-effect. There are known a number of depurants for such purposes, including
(1) affinity adsorbents, PA0 (2) porous resins such as Amberite XAD-7 sold by Rohm & Haas, PA0 (3) ion-exchange materials such as carboxymethyl cellulose and diethylaminoethyl agarose, and PA0 (4) porous inorganic materials such as porous glass and ceramics.
However, these depurants have several drawbacks. The porous resins and ion-exchange materials have low adsorptivity and poor adsorption specificity. They also adsorb albumin in body fluid to induce an anomalous change in osmotic pressure so that they cannot be used as a safe therapeutic member. The porous inorganic materials are not yet sufficient for practical use despite their relatively high adsorptivity and adsorption specificity.
The affinity adsorbents are generally classified into biological and physicochemical affinity adsorbents. The biological affinity adsorbents exhibit excellent adsorption specificity. However, most biological affinity adsorbents use a physiologically active high molecular weight compound as a ligand (material having affinity to a target material) and are thus expensive and difficult to gain. It is difficult to maintain the activity during preparation of adsorbents and columns, sterilization, stock storage, transportation, and shelf storage. A side effect must be taken into account because the biological affinity adsorbents can exert physiological functions other than affinity upon contact with blood. There is the likelihood that the ligand be released or dissolved away. Since most ligands are heterogeneous proteins, there occurs a problem of side effect due to antigenicity. On the other hand, the physicochemical affinity adsorbents have the advantages that they can be produced in a mass scale and their activity is stable. There are many physicochemical affinity adsorbents which are highly safe when contacted with blood.
A number of such adsorbents are known in the art, for example, porous materials having carboxyl group or sulfonate group at the surface as disclosed in Japanese Patent Application Kokai Nos. 56-147710, 57-56038, 57-75141, 57-170263, and 57-197294; hydrophilic carriers having a hydrophobic amino acid attached thereto as disclosed in Japanese Patent Application Kokai Nos. 57-122875, 58-15924, 58-165859, and 58-165861; hydrophilic carriers having denatured IgG attached thereto as disclosed in Japanese Patent Application Kokai Nos. 57-77624, 57-77625, and 57-156035; porous materials having methylated albumin attached thereto as disclosed in Japanese Patent Application Kokai Nos. 55-120875 and 55-125872; hydrophilic carriers having saccharide attached thereto as disclosed in Japanese Patent Application Kokai Nos. 57-134164 and 58-133257; and porous materials having purine base or pyrimidine base or saccharide phosphate attached thereto as disclosed in Japanese Patent Application Kokai Nos. 57-192560, 58-61752, and 58- 98142. In order to carry out extracorporeal circulation body fluid depuration therapy for the treatment of diseases, there is the need for an adsorbent which can more efficiently remove pathogenic substances than these prior art adsorbents while having less or little adverse effect on body fluid.